Compliance with oral administration is further compromised by the widespread recommendation that flucloxacillin should be taken on an empty stomach [1–4]. Department of Infectious Diseases, Christchurch Hospital, Christchurch, New Zealand, The ratio fed/fasting (geometric mean ± 90% CI) following 1000 mg oral flucloxacillin is also provided based on raw data, and modelled to steady-state. Caffeine was permitted only after the 4-hour blood sample and alcohol was forbidden until completion of the study day. Privacy Rather than focusing on administration on an empty stomach, it is more important that dosing is individualized according to known or suspected susceptibility to flucloxacillin, illness severity, and host characteristics. 2011, 130: 11-18. The data in the original publications cannot be accurately re-evaluated according to current pharmacodynamic end points as free flucloxacillin concentrations (i.e. Truth For Life is a qualified 501(c)(3) tax-exempt organization. BMC Cancer. LH has contributed to the protocol of the study and contributed to the manuscript. Differences in achievement of pharmacodynamic targets were minor and ranged from a small reduction in PTA for a free concentration target of greater than 0.5 mg/L for 30% of the dose interval, bioequivalence for a target of 50%, and non-inferiority for a target of 70%. Int J Epidemiol. 2011, 6: e28467-10.1371/journal.pone.0028467. For this patient group, bacteriostasis is probably all that is necessary. It is therefore vital for the growth and development, and the regeneration and repair of damaged tissues. 10.1016/S0895-4356(99)00144-4. Estimates obtained from BeggC are valid … In addition tests need sufficient power to perform optimal which may be relevant for concordance. Aliment Pharmacol Ther. The half-life (t1/2) was calculated from 0.693/k. Lu Y, Chen YQ, Guo YL, Qin SM, Wu C, Wang K: Diagnosis of invasive fungal disease using serum (1– –>3)-beta-D-glucan: a bivariate meta-analysis. 2014, 60: 651-659. 3. For example diagnostic data are often collected as part of daily clinical care and retrospectively analysed. 2011, 54: 1082-1090. 2003, 56: 943-955. Articles were eligible for inclusion if they systematically assessed the diagnostic accuracy of a test or biomarker and were published in English. 10.1016/j.jclinepi.2005.01.016. But, the results extracted from the panel covering all of the countries reflect that R&D expenditures cause the real income per capita to rise (Özcan, ArÕ, 2014). We advise authors of DTA reviews to try to avoid the introduction of publication bias and apply thorough methods for identifying primary studies, alongside regular searches in electronic biomedical databases. Available instantly. This could be the result of the increased awareness of the possible threat of publication bias in DTA reviews. 2012, 19: 349-357. Define et al.. et al. In 18 reviews (15.8%), the results of the publication bias assessment led to less confidence in the results. PLOS ONE promises fair, rigorous peer review, For the small subpopulation of patients infected with a strain of S. aureus with an MIC > 0.25 mg/L, the PTA simulations suggest a potential benefit of the fasting state, as there is a greater probability of achieving the target concentration for bacteriostasis (30% of the dose interval). Parekh-Bhurke S, Kwok CS, Pang C, Hooper L, Loke YK, Ryder JJ, Sutton AJ, Hing CB, Harvey I, Song F: Uptake of methods to deal with publication bias in systematic reviews has increased over time, but there is still much scope for improvement. For free concentrations exceeding 50% of these targets the fed state was at least bioequivalent to the fasting state. Suboptimal tests like Egger’s and Begg’s are frequently used, while the interpretation of the test results are rarely linked to the pooled results. Writing – original draft, Affiliations Administration is complicated by the requirement for frequent dosing, usually four times daily. 2012, 59: 517-520. Disagreements were resolved by discussion. Investigation of publication bias in meta-analyses of diagnostic test accuracy: a meta-epidemiological study. CRC Reef Research Centre. Serrated line: fed; continuous line: fasting. De deelstudies geven inzicht in het functieprofiel, taken en verantwoordelijkheden van zowel de Physician Assistants (PA’s) als de Verpleegkundig Specialisten (VS-en). (Deng et al., 2014; Postow et al., 2012). The lower limit of quantification was 0.2 mg/L for total flucloxacillin and 0.005 mg/L for free flucloxacillin. Gastrointest Endosc. 10.1016/j.gie.2011.09.016. 2011, 32: 1134-1142. Results for 8 hours post-dose and those predicted for steady state were similar. Publication bias was explicitly mentioned in 75 reviews (65.8%) and 47 of these had performed statistical methods to investigate publication bias in terms of small study-effects: 6 by drawing funnel plots, 16 by statistical testing and 25 by applying both methods. Additionally, if it was clinically important to reach a bactericidal target for all potentially infecting S. aureus strains, and for a larger percentage of the dose interval, as might be required in severe disease or in neutropenic sepsis, the fed state offers no disadvantage over the fasting state. 2011, 107: 659-667. Solomon et al, (2014). Brazzelli M, Lewis SC, Deeks JJ, Sandercock PA: No evidence of bias in the process of publication of diagnostic accuracy studies in stroke submitted as abstracts. On the first study day, volunteers were randomized so that half (n = 6) received the flucloxacillin after a high-fat high-calorie breakfast (fed state) and half received flucloxacillin on an empty stomach (fasting state). Dickersin K: The existence of publication bias and risk factors for its occurrence. The dotted lines indicate a p-value of 0.05. more than future funding models (Bachtler and Begg 2016). Finally, 114 DTA reviews were included for the current study. Evid Based Med. Methods to investigate publication bias are developed to investigate publication bias in meta-analyses [14]. Various models were considered based on visual examination of the raw concentration-time data for individuals, and for the amalgamated data using Monolix (lixoft.com/products/monolix). The apparent oral CL (CL/F, where F = oral availability) was calculated from Dose/AUC0–∞. Project administration, It has the same interpretation as Harrell's C for survival data (implemented in the rcorr.cens function of the Hmisc package).BeggC is restricted to Cox regression. A subsequent study using the same dose had similar findings, with mean peak total serum concentrations of 6.2 mg/L at 3 hours after administration with food and 11.4 mg/L at 1 hour after administration on an empty stomach [6]. Breast Cancer Res Treat. 2013, Vienna, Austria: R Foundation for Statistical Computing. J Gastrointest Surg. © 2021 BioMed Central Ltd unless otherwise stated. 2016). Papathanasiou ND, Boutsiadis A, Dickson J, Bomanji JB: Diagnostic accuracy of (1)(2)(3)I-FP-CIT (DaTSCAN) in dementia with Lewy bodies: a meta-analysis of published studies. It has the same interpretation as Harrell's C for survival data (implemented in the rcorr.cens function of the Hmisc package).BeggC is restricted to Cox regression. Hazem A, Elamin MB, Malaga G, Bancos I, Prevost Y, Zeballos-Palacios C, Velasquez ER, Erwin PJ, Natt N, Montori VM, Murad MH: The accuracy of diagnostic tests for GH deficiency in adults: a systematic review and meta-analysis. Carli, V, Hoven, CW, Wasserman, C. (2014) A newly identified group of adolescents at “invisible” risk for psychopathology and suicidal behavior: findings from the SEYLE study. Eur J Radiol. [19]. All urine was collected from 0 to 12 hours after taking flucloxacillin, the total urine volume recorded and an aliquot retained for determination of total flucloxacillin concentrations. The study of Deeks et al. Finally, it should not be assumed that the findings of this study extend to other isoxazolyl penicillins, but this too warrants further investigation. 2014 Update (2000). For comparision with Fig 4 in paper. W Annefloor van Enst. Breast Cancer Res Treat. Evidence from both in vitro and animal studies indicate that for bacteriostasis, an fT>MIC of 25–30% of the dosing interval is required for S. aureus and approximately 40% for streptococci [8,9]. Prior to the study each volunteer was screened by questionnaire, medical examination and blood testing to ensure there was no food intolerance, pregnancy, chronic illness, renal impairment (estimated GFR < 80 mL/min/1.73 m2) [12], liver dysfunction, malabsorption, or known intolerance of flucloxacillin. 2011, 38: 2040-2049. This may be associated with more upper gastrointestinal side effects and lead to some patients omitting doses around meal times and may be virtually unachievable in small children who often have variable eating patterns. Nursing Times. Several studies have indicated that breastfed children have a lower risk of childhood obesity than those who were not breastfed, while other studies have provided conflicting evidence. Intra- and inter-day coefficients of variation were < 10% over these concentration ranges. For statistical analyses, the summary RR and 95% CI were calculated using a random effects model. https://doi.org/10.1371/journal.pone.0199370.s001, https://doi.org/10.1371/journal.pone.0199370.s002. For a PTA for 30% of the dosing interval, food shifted the curve to the left for both 6- and 8-hour dosing. For both tests a significant result is an indication that the results might be affected by publication bias. Optimization could be achieved if prospective registration of diagnostic accuracy studies would be mandatory. This order was reversed on the second study day. Free flucloxacillin concentrations (geometric means) exceeded for 30%, 50% and 70% of 6- and 8-hour dose intervals in the fed and fasting state. Health Technol Assess. Contrary to what has been widely accepted since the 1970s, the results of this study indicate that taking flucloxacillin with food may not compromise effective flucloxacillin plasma concentrations in most circumstances. Eur J Heart Fail 11:292–298. A cohort of prospective diagnostic studies could be followed and the dissemination of study results may be compared to the study characteristics and results. https://doi.org/10.1371/journal.pone.0199370.g003. 10.2307/2533446. Relevant MIC90 of S. pyogenes (0.1 mg/L) and S. aureus (0.5 mg/L) are indicated by vertical serrated lines. In cases of disagreement between the results of a funnel plot and a test, all authors emphasized on the test results. BMC Medical Research Methodology 10.1373/clinchem.2013.218149. Validation, 2006, 25: 3443-3457. Sadigh G, Carlos RC, Neal CH, Dwamena BA: Ultrasonographic differentiation of malignant from benign breast lesions: a meta-analytic comparison of elasticity and BIRADS scoring. Egger M, Davey SG, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. | Jan 16, 2014. PLoS One. Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. 2006, 25: 1219-1238. AUC from 0 h until infinity (AUC0–∞) was assessed using the linear up/log down trapezoidal rule, with extrapolation to infinity using Clast/k, where Clast is the last measured concentration and k is the elimination rate constant. 10.1007/s11605-012-1827-4. 10.1530/EJE-11-0476. 10.1136/bmj.315.7109.629. The increase in childhood obesity is a serious public health concern. If the methods were lacking but the results of a publication bias assessment were described, it was also scored as an investigation of publication bias. However, the molecular mechanism for host type I IFN induction following local radiation has not yet been defined. R Core Team: R: A Language and Environment for Statistical Computing. Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis. 10.1373/clinchem.2008.108993. The dots in this plot together look like an inverted funnel. The 95% CIs include both inter-individual and inter-occasion variability. Sci. Edited by: Deeks JJ, Bossuyt PM, Gatsonis C. 2010, Oxford, United Kingdom: The Cochrane Collaboration, 46-47. 10.1002/sim.2380. 10.1016/j.acra.2011.10.018. The results of investigation of publication bias were discussed in 25 out of 47 reviews that assessed publication bias. Clin Chem. Out of 1,335 references, 114 reviews could be included. J Urol. Wang W, Li Y, Li H, Xing Y, Qu G, Dai J, Liang Y: Immunodiagnostic efficacy of detection of Schistosoma japonicum human infections in China: a meta analysis. The different models assessed therefore included zero-and first-order absorption with or without Tlag, and one- and two-compartments. Google Scholar. A two-compartment model was excluded because of no suggestive visual evidence in the individual concentration-time curves, and by higher values for the Akaike information criteria (AIC) compared with a one-compartment model using PKSolver. Learn More Submit Now 2004, 141: 477-478. Probability of target attainment (PTA) for 30%, 50% and 70% of 6- and 8-hour dose intervals with flucloxacillin 1000 mg orally modelled to steady-state using zero-order absorption for a range of MICs. 10.1016/j.gie.2011.07.026. 10.1001/jama.1990.03440100097014. It is usually recommended that flucloxacillin is given on an empty stomach. Other potential advantages of taking flucloxacillin with food include convenience, improved compliance and reduction in adverse effects such as nausea. Begg CB, Mazumdar M: Operating characteristics of a rank correlation test for publication bias. In addition, the interpretation of the results of the various methods and incorporating those results in the formulation of the conclusions of the review is even more challenging. Article  We first piloted the form among all team members. Flucloxacillin taken with food was associated with a significant reduction in free and total AUC and Cmax, and a prolonged Tmax, as shown with total flucloxacillin concentrations in previous studies [5,6]. Zhang L, Zong ZY, Liu YB, Ye H, Lv XJ: PCR versus serology for diagnosing Mycoplasma pneumoniae infection: a systematic review & meta-analysis. / Procedia - Social and Behavioral Sciences 195 ( 2015 ) 501 – 507 3. The results were modelled for both 6- and 8-hourly dosing, as both regimens have been recommended, and because in practice it is almost impossible to dose precisely every 6 hours. Relevant MIC90 of S. pyogenes (0.1 mg/L) and S. aureus (0.5 mg/L) are indicated by vertical serrated lines. No, Is the Subject Area "Pharmacodynamics" applicable to this article? Dong MJ, Zhao K, Liu ZF, Wang GL, Yang SY, Zhou GJ: A meta-analysis of the value of fluorodeoxyglucose-PET/PET-CT in the evaluation of fever of unknown origin. In 8 reviews the authors used more than one test to examine publication bias. Writing – review & editing, Affiliations ML, RS and LH are all involved in the Cochrane DTA working group. In reviews that had constructed a funnel plot and performed a test, the conclusions were based on the combination (funnel plot and test) or only on the test. Acad Radiol. This work is highly significant because it studies a very large population of 949 youths (8–22 y, 428 males and 521 females) using the diffusion-based structural connectome of the brain, identifying novel sex differences. 10.1002/art.33379. BMC Med Res Methodol 14, 70 (2014). Prior to administration of flucloxacillin on the study days, volunteers were not allowed food for 8 hours but had free access to water. Concordance of the Begg and Egger tests was significantly better depending on the number of included studies (OR 1.09; 95% CI 1.03 to 1.10). Ioannidis JP: Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials. J Clin Epidemiol. 2012, 5: 15-23. Directed by Hallvard Bræin. Cell division is the process by which new cells are made. Meader N, Mitchell AJ, Chew-Graham C, Goldberg D, Rizzo M, Bird V, Kessler D, Packham J, Haddad M, Pilling S: Case identification of depression in patients with chronic physical health problems: a diagnostic accuracy meta-analysis of 113 studies. 2007; Otto et al. Flucloxacillin 1000 mg orally was given to 12 volunteers, after a standardised breakfast and while fasting, on two separate occasions. The tests were performed as follows: Begg’s test: rank correlation of the lnDOR with the variance of the lnDOR [11]; Egger’s test: linear regression of lnDOR with the standard error of the lnDOR weighted by the inverse variance of the lnDOR [12]; Deeks’ test: linear regression of lnDOR with 1/ESS1/2 weighted by the ESS [19]. 10.1258/ar.2011.110115.